Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma
Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of PIK3CA mutations. In low grad...
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| Veröffentlicht in: | Virchows Archiv : an international journal of pathology 2014-08, Vol.465 (2), p.193-198 |
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| description | Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of
PIK3CA
mutations. In low grade serous ovarian cancer,
KRAS
and
BRAF
mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of
KRAS
,
NRAS
, and
BRAF
hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of
KRAS
,
NRAS
, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of
KRAS
,
NRAS,
and
BRAF
hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of
KRAS
in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of
NRAF
(exons 2, 3, 4) or
BRAF
(exon 15). The median age of women with a
KRAS
mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a
KRAS
mutation occurs in codon 2 exon 2.
NRAS
and
BRAF
mutations were not found. |
| doi_str_mv | 10.1007/s00428-014-1599-1 |
| format | Article |
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PIK3CA
mutations. In low grade serous ovarian cancer,
KRAS
and
BRAF
mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of
KRAS
,
NRAS
, and
BRAF
hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of
KRAS
,
NRAS
, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of
KRAS
,
NRAS,
and
BRAF
hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of
KRAS
in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of
NRAF
(exons 2, 3, 4) or
BRAF
(exon 15). The median age of women with a
KRAS
mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a
KRAS
mutation occurs in codon 2 exon 2.
NRAS
and
BRAF
mutations were not found.</description><identifier>ISSN: 0945-6317</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s00428-014-1599-1</identifier><identifier>PMID: 24889043</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adenocarcinoma, Clear Cell - genetics ; Adult ; Aged ; Codon - genetics ; DNA Mutational Analysis ; DNA, Neoplasm - genetics ; Exons - genetics ; Female ; GTP Phosphohydrolases - genetics ; Humans ; Incidence ; Medicine ; Medicine & Public Health ; Membrane Proteins - genetics ; Middle Aged ; Mutation ; Original Article ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Pathology ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins - genetics ; Retrospective Studies ; Sequence Analysis, DNA</subject><ispartof>Virchows Archiv : an international journal of pathology, 2014-08, Vol.465 (2), p.193-198</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-2d0cf37904c16fa549f31c3d7f380f22df8729fc01de1e1964a884e2239cea603</citedby><cites>FETCH-LOGICAL-c471t-2d0cf37904c16fa549f31c3d7f380f22df8729fc01de1e1964a884e2239cea603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00428-014-1599-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00428-014-1599-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24889043$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zannoni, Gian Franco</creatorcontrib><creatorcontrib>Improta, Giuseppina</creatorcontrib><creatorcontrib>Chiarello, Gaia</creatorcontrib><creatorcontrib>Pettinato, Angela</creatorcontrib><creatorcontrib>Petrillo, Marco</creatorcontrib><creatorcontrib>Scollo, Paolo</creatorcontrib><creatorcontrib>Scambia, Giovanni</creatorcontrib><creatorcontrib>Fraggetta, Filippo</creatorcontrib><title>Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma</title><title>Virchows Archiv : an international journal of pathology</title><addtitle>Virchows Arch</addtitle><addtitle>Virchows Arch</addtitle><description>Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of
PIK3CA
mutations. In low grade serous ovarian cancer,
KRAS
and
BRAF
mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of
KRAS
,
NRAS
, and
BRAF
hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of
KRAS
,
NRAS
, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of
KRAS
,
NRAS,
and
BRAF
hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of
KRAS
in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of
NRAF
(exons 2, 3, 4) or
BRAF
(exon 15). The median age of women with a
KRAS
mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a
KRAS
mutation occurs in codon 2 exon 2.
NRAS
and
BRAF
mutations were not found.</description><subject>Adenocarcinoma, Clear Cell - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Codon - genetics</subject><subject>DNA Mutational Analysis</subject><subject>DNA, Neoplasm - genetics</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>Humans</subject><subject>Incidence</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Membrane Proteins - genetics</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Original Article</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Pathology</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Proto-Oncogene Proteins p21(ras)</subject><subject>ras Proteins - genetics</subject><subject>Retrospective Studies</subject><subject>Sequence Analysis, DNA</subject><issn>0945-6317</issn><issn>1432-2307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kE1LxDAQhoMo7rr6A7xIwIsHqzNJ2ibHdfELv_DrHGKaSKXbarIV_Pdm3VVE8JIE8sw7Mw8h2wgHCFAeRgDBZAYoMsyVynCFDFFwljEO5SoZghJ5VnAsB2QjxhcAhhKLdTJgQkoFgg_J7VU_M7O6a01DY3r1kXaeXtyN7_fp9ddp2ooe3Y1PaN3S11BPTfigtnEmUOuahnbvJtSmpdYEW7fd1GySNW-a6LaW94g8nhw_TM6yy5vT88n4MrOixFnGKrCel2kKi4U3uVCeo-VV6bkEz1jlZcmUt4CVQ4eqEEZK4RjjyjpTAB-RvUXua-jeehdnelrH-UimdV0fNeY5AuNFIRK6-wd96fqQVp5TQhWQS8UShQvKhi7G4LxerqsR9Ny3XvjWybee-9aYanaWyf3T1FU_Fd-CE8AWQExf7bMLv1r_m_oJ_UKHrg</recordid><startdate>20140801</startdate><enddate>20140801</enddate><creator>Zannoni, Gian Franco</creator><creator>Improta, Giuseppina</creator><creator>Chiarello, Gaia</creator><creator>Pettinato, Angela</creator><creator>Petrillo, Marco</creator><creator>Scollo, Paolo</creator><creator>Scambia, Giovanni</creator><creator>Fraggetta, Filippo</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20140801</creationdate><title>Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma</title><author>Zannoni, Gian Franco ; Improta, Giuseppina ; Chiarello, Gaia ; Pettinato, Angela ; Petrillo, Marco ; Scollo, Paolo ; Scambia, Giovanni ; Fraggetta, Filippo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-2d0cf37904c16fa549f31c3d7f380f22df8729fc01de1e1964a884e2239cea603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenocarcinoma, Clear Cell - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Codon - genetics</topic><topic>DNA Mutational Analysis</topic><topic>DNA, Neoplasm - genetics</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>Humans</topic><topic>Incidence</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Membrane Proteins - genetics</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Original Article</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Pathology</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Proto-Oncogene Proteins p21(ras)</topic><topic>ras Proteins - genetics</topic><topic>Retrospective Studies</topic><topic>Sequence Analysis, DNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zannoni, Gian Franco</creatorcontrib><creatorcontrib>Improta, Giuseppina</creatorcontrib><creatorcontrib>Chiarello, Gaia</creatorcontrib><creatorcontrib>Pettinato, Angela</creatorcontrib><creatorcontrib>Petrillo, Marco</creatorcontrib><creatorcontrib>Scollo, Paolo</creatorcontrib><creatorcontrib>Scambia, Giovanni</creatorcontrib><creatorcontrib>Fraggetta, Filippo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Virchows Archiv : an international journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zannoni, Gian Franco</au><au>Improta, Giuseppina</au><au>Chiarello, Gaia</au><au>Pettinato, Angela</au><au>Petrillo, Marco</au><au>Scollo, Paolo</au><au>Scambia, Giovanni</au><au>Fraggetta, Filippo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma</atitle><jtitle>Virchows Archiv : an international journal of pathology</jtitle><stitle>Virchows Arch</stitle><addtitle>Virchows Arch</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>465</volume><issue>2</issue><spage>193</spage><epage>198</epage><pages>193-198</pages><issn>0945-6317</issn><eissn>1432-2307</eissn><abstract>Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of
PIK3CA
mutations. In low grade serous ovarian cancer,
KRAS
and
BRAF
mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of
KRAS
,
NRAS
, and
BRAF
hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of
KRAS
,
NRAS
, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of
KRAS
,
NRAS,
and
BRAF
hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of
KRAS
in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of
NRAF
(exons 2, 3, 4) or
BRAF
(exon 15). The median age of women with a
KRAS
mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a
KRAS
mutation occurs in codon 2 exon 2.
NRAS
and
BRAF
mutations were not found.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24889043</pmid><doi>10.1007/s00428-014-1599-1</doi><tpages>6</tpages></addata></record> |
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| ispartof | Virchows Archiv : an international journal of pathology, 2014-08, Vol.465 (2), p.193-198 |
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| subjects | Adenocarcinoma, Clear Cell - genetics Adult Aged Codon - genetics DNA Mutational Analysis DNA, Neoplasm - genetics Exons - genetics Female GTP Phosphohydrolases - genetics Humans Incidence Medicine Medicine & Public Health Membrane Proteins - genetics Middle Aged Mutation Original Article Ovarian cancer Ovarian Neoplasms - genetics Pathology Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins p21(ras) ras Proteins - genetics Retrospective Studies Sequence Analysis, DNA |
| title | Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma |
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